3/3 September 2017 Volume 3 · Supplement 3 · September 2017 Journal of Virus Eradication ISSN 2055-66-40 – Print | ISSN 2055-66-59 – Online An online open-access journal published by Mediscript Ltd www.viruseradication.com Editors Jintanat Ananworanich (USA) Abstracts of the HIV Cure and Reservoir Margaret Johnson (UK) Sabine Kinloch-de Loës (UK) Symposium 2017 Editorial Board 11–12 September 2017 Nicolas Chomont (Canada) Ghent, Belgium Steven Deeks (USA) Geoff Dusheiko (UK) Stably integrated HIV inside the host cell genome is considered the final Sarah Fidler (UK) Paul Griffiths (UK) hurdle to cure one of the most important infectious diseases humans have ever Alain Lafeuillade (France) faced. The latent HIV reservoir is able to refuel infection once the treatment is Nelson Michael (USA) Jürgen Rockstroh (Germany) stopped and therefore a better understanding of both the composition and the Irini Sereti (USA) size of the reservoir is important to aid the development of cure strategies as Janet Siliciano (USA) well as to monitor the efficacy of therapeutic interventions to reduce the HIV Robert Siliciano (USA) Guido Silvestri (USA) reservoir. Our symposium will comprehensively summarise the state of the art Linos Vandekerckhove (Belgium) in HIV cure strategies and diagnostic tools to monitor therapeutic interventions Editorial Panel and an international expert panel will guide the audience through the latest David Asboe (UK) developments in the HIV cure field, focusing on reservoir characterisation and Georg Behrens (Germany) novel clinical strategies to achieve HIV cure. Monsef Benkirane (France) Michael R Betts (USA) Charles Boucher (Netherlands) David Cooper (Australia) Zeger Debyser (Belgium) Jean-Francois Delfraissy (France) Lucy Dorrell (UK) Daniel Douek (USA) Caroline Foster (UK) Graham Foster (UK) John Frater (UK) Brian Gazzard (UK) Anna Maria Geretti (UK) Carlo Giaquinto (Italy) Marie-Lise Gougeon (France) George Hanna (USA) Daria Hazuda (USA) Andrew Hill (UK) Ilesh Jani (Mozambique) Rowena Johnston (USA) Jerome Kim (USA) Richard Koup (USA) Nagalingeswaran Kumarasamy (India) Alan Landay (USA) Clifford Leen (UK) Yves Lévy (France) Sharon Lewin (Australia) Hermione Lyall (UK) Michael Malim (UK) Gail Matthews (Australia) Veronica Miller (USA) Cristiana Oprea (Romania) Melanie Ott (USA) Carlo Perno (Italy) Nittaya Phanuphak (Thailand) Guido Poli (Italy) Christina Psomas (France) Sarah Read (USA) Doug Richman (USA) Christine Rouzioux (France) Asier Saez-Cirion (France) Serena Spudich (USA) Claire Thorne (UK) Victor Valcour (USA) Carine Van Lint (Belgium) Jan Van Lunzen (Germany) i Volume 3 · Supplement 3 · September 2017 Journal of Virus Eradication ISSN 2055-66-40 – Print | ISSN 2055-66-59 – Online An online open-access journal published by Mediscript Ltd www.viruseradication.com Aims and objectives Disclaimer The aim of this journal is to provide a specialist, open access The Publisher, Editors and Authors cannot be held responsible forum and fast-track pathway to publish work in the rapidly for errors or any consequences arising from the use of the developing field of virus eradication, particularly of HIV, HBV information contained in this Journal; the views and opinions and HCV. 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Editorial office Journal of Virus Eradication If you would like any further information, please contact us at: [email protected] Published by: Mediscript Ltd Editorial Director: Fatima Patel Editorial Office: Fiona Creagh Mediscript Ltd, 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD, UK T: 44 (0)208 446 8898 · E: [email protected] ISSN 2055-66-40 (Print) · ISSN 2055-66-59 (Online) ii Volume 3 · Supplement 3 · September 2017 Journal of Virus Eradication ISSN 2055-66-40 – Print | ISSN 2055-66-59 – Online An online open-access journal published by Mediscript Ltd www.viruseradication.com CONTENTS ■ ORAL PRESENTATIONS 1 ■ POSTER PRESENTATIONS 4 iii Journal of Virus Eradication 2017; 3 (Supplement 3): 1–5 ORAL ABSTRACTS Oral abstracts of the HIV Cure and Reservoir Symposium 2017 O1 decitabine-induced HIV-1 reactivation occurred at specific and reproducible CpG positions that differed depending on the two cell Towards a block-and-lock strategy: LEDGINs hamper lines studied. Interestingly, a site comprising one of this hotspot for the establishment of a reactivation competent decitabine-induced demethylation was shown to bind UHRF1, only reservoir in one of cell line. Treatment with decitabine caused a decreased in vivo UHRF1 recruitment to the 5’LTR. UHRF1 knockdown using RNA Gerlinde Vansant, Lenard S Vranckx, Irena Zurnic, Suha Saleh, interference and pharmacological approach showed increased levels Anne Bruggemans, Frauke Christ, Zeger Debyser of HIV-1 production in latently-infected cells and of HIV-1 transcription Laboratory of Molecular Virology and Gene Therapy, Department of in ex vivo cell cultures from cART-treated aviremic HIV+ patients, Pharmacological and Pharmaceutical Sciences, KU Leuven, respectively. Belgium. UHRF1 has not previously been identified as a regulator of HIV latency Background: Persistence of latent provirus is the main barrier towards and might thus constitute a new therapeutic target for HIV cure a cure for HIV. We propose a novel strategy to reduce the HIV reservoir strategies. by drug-induced retargeting of HIV integration. A novel class of integration inhibitors, LEDGINs, inhibits the interaction between HIV integrase (IN) and the LEDGF/p75 cofactor, the main determinant of integration site selection. This results in an allosteric inhibition of HIV O3 IN (early effect). Moreover, when present during production, progeny virus displays morphological and replication irregularities (late effect). Heme-arginate as a latency-reversing agent for HIV-1 Methods: Integration sites were sequenced using 454 cure pyrosequencing. To evaluate reactivation potential, cell lines were Michaela Madlenakova1,2, Prakash Shankaran1, Vera Hajkova1,2, infected with a double-reporter virus and LEDGIN was added during David Jilich3,, Ladislav Machala3, Pavel Martasek2, Zora Melkova1,2 infection (early effect) or during production of the virus (late effect). 1Department of Immunology and Microbiology, Charles University, Cells were reactivated and analyzed by FACS. In a multiple round st 2 + 1 Faculty of Medicine, Prague, Czech Republic, BIOCEV, experiment, primary activated CD4 T cells were infected with wild Biotechnology and Biomedicine Center of the Academy of Sciences type NL4.3 virus in the presence of LEDGIN or RAL. Cells were and Charles University, Vestec, Czech Republic, 3AIDS Center, Na reactivated and virus production was measured by p24 ELISA. Bulovce Hospital, Prague, Czech Republic Results and conclusions: LEDGIN-mediated inhibition of the LEDGF/p75-IN interaction blocks replication and relocates integration Current antiretroviral therapy does